Promising CLL Treatments: A Bcl-2 Inhibitor Update

Published on
February 21, 2014

Topics include:
Treatment

Dr. John Seymour, a CLL researcher, shares an update about an ongoing trial using the Bcl-2 inhibitor ABT-199, which received a dose modification following safety concerns. Dr. Seymour explains Phase I trial data that demonstrates the therapy's balance of safety and efficacy as well its promising potential for combination with other agents.

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Andrew Schorr:

Hello and welcome to Patient Power. I'm Andrew Schorr. At the 2013 meeting of the American Society
of Hematology, thousands of doctors and researchers from around the world gathered
to discuss the latest in many blood?related cancers including chronic
lymphocytic leukemia, CLL.

A lead investigator for one promising drug, ABT-199, is
Dr. John Seymour from Australia. We
spoke to him to get an update on ABT-199.

Dr. Seymour:

The drug's ABT-199. We're still completing the Phase I study so
the dose escalation. We've got to a
point where we're now in safety expansion at the 400 milligram dose level, so
there's a dose that's been identified that appears to have a very good balance
of safety and effectiveness—and probably for patients or potential patients who
are thinking about this or trial participation really two important
messages.

The first is that the effectiveness, the overall response rate,
is holding up very well. On the current
analysis to be presented here, it's an 84 overall response rate with 23 percent
complete remissions including a few patients assist on local laboratories that
are negative MID.

So the safety message is the second part. There, as we've spoken with you previously,
there had been a signal of concern about tumor lysis syndrome, so with
modifications to a more gradual step-wise dose escalation and very vigilant
prophylaxis, there have not been any more cases of tumor lysis syndrome that's
seen. So we're cautious but optimistic
that that gradual dose escalation scheme, beginning at a dose of 20 milligrams
on the first day with three sequential steps to the 400 milligram dose level,
appears to be safe.

Andrew Schorr:

We asked Dr. Seymour if ABT?199 could be combined with other
drugs for even more effectiveness.

Dr. Seymour:

Based on what we know from animal studies and test tube
combinations that have substantial amount of promise. The toxicity that we're seeing with ABT-199
on its own makes that an appealing and likely safe combination, and studies
with, at the moment, monoclonal antibodies, both rituximab and in a separate
study obinutuzumab, have begun. So hopefully we'll soon have data to be able to
see if the combination is safe and potentially is more effective.

The hope is that if we continue to see high complete remission
rates, that we'll then be able to use a limited period of treatment rather than
requiring indefinite ongoing therapy, which is currently the design of the
study with ABT-199 as a single agent.

Andrew Schorr:

With treatments changing in CLL and others in late stage
research, we asked Dr. Seymour whether he would recommend that patients
consider participating in a clinical trial.

Dr. Seymour:

It's so hard to make any of those comparisons. For investigators, for patients the landscape
is phenomenally encouraging. There are a
number of classes of drugs that work in different ways, many of them oral. One of the things to consider is not just
short?term convenience, that's probably not the right word for it, but the
logistic simplicity in the short term but with many agents the potential need
for indefinite treatment. And some of these agents have what are low grade but
perhaps persistent toxicity. So we need
to look at the total experience both in terms of effectiveness and potential
adverse effects as well very realistically the total financial cost for
patients as well as for the broader community.

So there are multiple elements to be considered, but we're
still very much in the phase of learning how these components may fit
together.

Andrew Schorr:

We appreciate having Dr. John Seymour with us once again
on Patient Power. I'm sure we'll hear
from him again as there's more news to report on ABT-199 and other promising
therapies for CLL, so be sure to be signed up for alerts on our website so we
can let you know whenever we post something new.

I'm Andrew Schorr. Thank
you for joining us. Remember, knowledge
can be the best medicine of all.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.